tbuckley/cabot-search huggingface dataset:
Racial differences in prognostic role of white blood cell ratios in gastrointestinal stromal tumors.
Authors: Nikita Chintapally, Markos Kashiouris, Zhonghua Liu, Enrico Bautista, Aalisha Desai, Jamie Kayla Haber, Sosipatros Alexandros Boikos
Journal: Journal of Clinical Oncology (2023)

e23507 Background: Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors with an estimated 3,300 to 6,000 new cases per year in the United States. Per SEER database, significant racial disparity exists with an incidence rate twice as high for African Americans as compared to Whites. Currently, parameters used in stratification of disease risk can only be determined by postoperative histopathological evaluation. Cancer-related inflammation is linked to different stages of tumor development so markers found in peripheral blood have been studied as surrogates. We present a study comparing the predictive prognostic ability of preoperative serum inflammatory markers in primary untreated GIST and highlight the differences between Black and White patients. Methods: This is a retrospective analysis of 149 patients who underwent operative resection of primary untreated GIST. Preoperative blood samples were used for the analysis. Patients were excluded if they showed clinical signs of infection during time of pre-operative blood sampling or had non-GIST synchronous malignancy. Clinicopathological data was obtained from patient chart review and logistic regression models were used to evaluate data. There is ongoing next-generation sequencing data analysis. Results: 149 patients were included: 80 (53.7%) Black, 43 (28.9%) White, 26 (17.5%) were other. The mean values for neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR) were 3.62 (SD 3.07), 191.55 (SD 119.15), and 0.47 (SD 0.49) respectively. On univariate analysis NLR and PLR were significant prognostic indicators of high and intermediate risk GISTs per the National Institute of Health (NIH) categories [NLR p = 0.008, PLR p = 0.007]. Upon subgroup analysis, NLR and PLR showed the highest statistical significance for predictors of high and intermediate risk GISTs among the Black patient population [NLR odds ratio (OR) 2.685; 95% confidence interval (CI) 0.976-7.381; p = 0.05 and PLR OR 1.792; 95% CI 1.054-3.049; p = 0.031]. The same was not shown to be true for the White patient population. 11 out 149 patients progressed since diagnosis of which 8 were Black and 3 White. 7 were in the high risk category, 3 in low risk and 1 in intermediate risk with an overall mean NLR and PLR 5.25 and 244 respectively. The average time to progression was noted to 28 months. Conclusions: The NLR and PLR are easily obtainable and cost-effective indexes which have the prognostic ability to serve as surrogates for high and intermediate risk GISTs. They appear to be more predictive in the Black patient population than in White. Further study is warranted for incorporation into risk stratification systems.
D-CRSE: Diminishing chemotherapy related side effects through patient education.
Authors: Hannah Dailey, Shelby A. Labe, Gavin Jones, Joanna Bhasker, Rhea Kanwar, Sonia Hafiz, Madison Crago, Britney Fitzgerald, Daniella Mikhail, Junjia Zhu, Monali K. Vasekar
Journal: Journal of Clinical Oncology (2023)

e24148 Background: Patient (pt) education materials regarding self-management of cytotoxic chemotherapy related side effects are lacking at Penn State Cancer Institute (PSCI), resulting in patients using disreputable sources. We created a brochure that educates patients on common side effects, tools to address the problems themselves, information on when to contact their oncologist, and guidance on when to visit the ED. The aim of our pilot study is to evaluate the feasibility at PSCI and subsequently improve pt related outcomes and quality of life through pt education. Methods: Chemotherapy naïve pts with breast or gastrointestinal (GI) cancer were enrolled from November 2021-December 2022. At the baseline visit, pts were consented, given the brochure and asked to complete surveys. The Emotional Thermometer Scale (ETS) evaluates mental health, measuring distress, anxiety, depression, and anger while the Memorial Symptom Assessment Scale (MSAS) evaluates symptoms commonly seen with chemotherapy. MSAS means were also broken down into physical, psychological, and global distress index (GDI) subsets. Pts filled out the same surveys at their 6 and 12 week visits to assess change over time. Results: 40 pts completed the baseline surveys, and 36 of them had at least one additional visit. Some key demographics were: 82.2% female, 17.8% male, 22.2% GI cancer (71.4% colonic adenocarcinoma, 14.3% rectal adenocarcinoma, 14.3% anal squamous cell carcinoma), 77.8% breast cancer (81.8% ductal carcinomas, 9.1% lobular carcinomas, 9.1% invasive metaplastic carcinoma, 52.5% ER+, 42.5% PR+, 22.5% HER2+), and 27.5% of patients underwent concurrent therapies with chemotherapy. Table 1 summarizes the mean score comparisons from baseline to 6 and 12 weeks for the ETS and MSAS. We observed significantly decreased psychological symptoms at week 12 compared to baseline (p = 0.023), while physical symptoms did not change significantly (p = 0.21). Conclusions: We successfully conducted a pilot study distributing a standardized educational brochure, thus demonstrating feasibility of this intervention. Measured psychological symptoms decreased over time, while physical symptoms did not, which aligns with side effect progression from cumulative chemotherapy burden. We plan to expand standardized pt education materials to other cancer types, incorporate digital educational tools, and further explore pt education barriers. Clinical trial information: NCT04694794 .[Table: see text]
Safety of checkpoint inhibitors in older patients with genitourinary cancers.
Authors: Brian Hemendra Ramnaraign, Neil Jigish Patel, Jonathan Alexander Chatzkel, Kathryn Hitchcock, Robert Zlotecki, Padraic O'Malley, Paul Crispen
Journal: Journal of Clinical Oncology (2023)

12059 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the care of patients with genitourinary (GU) cancers however many of the clinical trials that have led to the approval of ICIs in GU cancers often have low enrollments of older patients aged 65 and above for which safety data in this cohort is limited. Methods: A retrospective study was performed that included all patients aged 65 and older with kidney, bladder, and upper tract urothelial carcinoma (UTUC), who were treated at the University of Florida Health Cancer Center between January 2018 and September 2022, and received at least one dose of ICI (pembrolizumab, nivolumab, ipilimumab with nivolumab, avelumab, or atezolizumab). Data was collected on all documented immune related adverse events (irAEs) that were deemed attributable to the checkpoint inhibitor by the treating provider. The grading of toxicities was determined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: We identified a total of 139 patients who met the inclusion criteria of our study. The ages of patients ranged from 65 to 93 and the median age was 74. Females accounted for 31 patients (22%) while 108 patients (78%) were male. There were 56 patients (40%) with bladder cancer, 58 patients (42%) with kidney cancer, and 25 patients (18%) with UTUC. An irAE was documented in 76 patients (55%) while 63 patients (45%) had no documented irAE. Patients were categorized by the highest grade of toxicity experienced. A Grade 1 toxicity was found in 15 patients (11%), while a grade 2 toxicity was found in 41 patients (29%), with 18 patients (13%) having a grade 3 toxicity, and 2 patients (1%) experiencing a grade 4 toxicity. There were no documented grade 5 toxicities, i.e. no deaths were directly attributed to treatment. We found that 27 patients (19%) required either oral or intravenous steroids to manage their irAE. Discontinuation of treatment due to an irAE was observed in 16 patients (12%). Inpatient hospitalization due to an irAE occurred in 12 patients (9%). Conclusions: Our study demonstrates that the majority of patients aged 65 and older either have no irAEs or developed mild irAEs when treated with ICIs. Severe and life-threatening adverse events are uncommon, rarely require hospital admission, and did not lead to any deaths. This study should help to provide valuable information on the safety of checkpoint inhibitors in older patients with GU cancers and assist in the shared decision-making process for cancer treatment. [Table: see text]
Prospective dynamic sampling and molecular residual disease monitoring to predict clinical outcomes for patients with unresectable, locally advanced non-small cell lung cancer undergoing radical radiotherapy.
Authors: Jia-Tao Zhang, Yi Pan, Xuan Gao, Zhi-yong Chen, Bingfa Yan, Pei-Xin Tan, Xiao-Rong Yang, Hui Lin, Hong-Hong Yan, Song Dong, Bin-Chao Wang, Jin-Ji Yang, Hai-Yan Tu, Xue-Ning Yang, Wenzhao Zhong, Xuefeng Xia, Xin Yi, Qing Zhou, Yi-Long Wu
Journal: Journal of Clinical Oncology (2023)

8549 Background: The role of molecular residual disease (MRD) detection in non-small cell lung cancer (NSCLC) patients after definitive resection has been progressively elaborated. However, the dynamic patterns of circulating tumor DNA (ctDNA) during and after radical radiotherapy (RT) remain unclear but are critical for detecting MRD in this context. Methods: We enrolled 139 patients with locally advanced NSCLC treated with radical RT in this prospective study. And 761 blood samples were successfully detected by ctDNA-MRD assay at different preset timepoints before, during and after RT. Results: There was a declining trend in ctDNA concentrations of “during RT” time point (RT reached 40 Gy) relative to those after RT. Patients with negative ctDNA of “during RT” and “after RT” time points may indicate an early response to RT, and had better progression-free survival (PFS) than those with late response to RT(ctDNA clearance only at “after RT” time point, HR = 0.30, 95%CI: 0.12-0.75, p = 0.004). Moreover, patients with both negative ctDNA of “during RT” and “after RT” time points could not benefit from consolidation therapy (HR = 0.72, 95%CI: 0.29-1.78, p = 0.478), while patients with any positive ctDNA of them could (HR = 0.59, 95%CI: 0.38-0.93, p = 0.023).The sensitivity of longitudinal MRD was 97.8% and only two patients with local progression were overlooked. The 2-year cancer-specific PFS of patients with longitudinal undetectable MRD was 88.4%, which corresponds to the potentially cured population. For patients with only blood-informed MRD detection, the sensitivity and median lead time of longitudinal MRD were 97.7% and 3.9 months, respectively, which indicating the feasibility and efficacy of blood-informed MRD detection strategy. Conclusions: These data shed new light on the ctDNA-MRD detection for localized NSCLC patients who received radical RT.
Demographics of the tumor formerly known as bronchiolo-alveolar carcinoma.
Authors: Andrew Luker, Beau Hsia, Xinxin Wu, Peter T. Silberstein, Darby Keirns
Journal: Journal of Clinical Oncology (2023)

e20604 Background: Bronchiolo-alveolar carcinoma (BAC) is a rare subtype of non-small cell lung cancer of the lung periphery, often characterized by lepidic growth. Although BAC has undergone various reclassifications in recent years, International Classification of Disease codes still classifies these subtypes using the same codes that previously belonged to BAC. Changing diagnostic criteria and other factors cause BAC to be among the most overdiagnosed forms of lung cancer and thus a demographic study could provide insight into trends. Methods: A retrospective cohort analysis utilizing the National Cancer Database (NCDB) from 2004 – 2020 included patients with malignant forms of BAC (Invasive mucinous adenocarcinoma, mixed invasive mucinous, and nonmucinous adenocarcinoma) confirmed through histology. Demographic factors such as sex, age, race, Hispanic status, median household income, insurance status, facility type, county population, distance from facility, and Charlson Deyo score were analyzed by descriptive statistics and incidence trends. Results: In total, 12,607 patients were identified in the database with a confirmed diagnosis of BAC between 2004 – 2020. The number of cases per year remained steady (mean = 565.4) until 2018. From 2018 to 2020, the average number of diagnoses per year was 1575.0. The average age of diagnosis was 69.3 years (SD = 10.7, range = 10 to &gt; 90 years). 58.1% of the cases were female patients. The top primary sites were the lower and upper lobes (46.2% and 39.9% respectively). The majority (59.2%) had Charlson-Deyo comorbidity scores of 0. Most cases occurred in Non-Hispanic White persons (86.8%). More patients were in the top quartile of income earners (34.0%) compared to those in lower quartiles. Medicare was the insurance provider for most patients (65.0%). More patients were diagnosed in counties with a population over 1 million (52.4%). More patients were treated in comprehensive community cancer programs (38.1%) followed closely by academic cancer programs (35.2%). Patients lived an average of 31.6 miles (SD = 113.0, range = 0.1 – 2390.7) from the treatment facility. Conclusions: This is the first NCDB analysis on the demographics of BAC. The sudden rise in cases per year in 2018 aligns with the changing pathologic and histologic definitions for BAC. A 2006 review of BAC found that 50-70% of cases occur in female patients, similar to our results. The majority of BAC patients tend to be non-Hispanic and White with a primary site diagnosis in the lower lobe, followed by the upper lobe. BAC patients are more likely to be in the top income quartile, live in densely-populated metropolitan areas, and receive treatment in a non-academic program. Further research is needed to better understand the impact of demographic, socioeconomic, and environmental factors on the diagnosis and prognosis of BAC, especially because its diagnostic criteria have changed recently.
Preliminary dose escalation results from a first-in-human, phase I/II study of GB263T, a novel EGFR/cMET/cMET trispecific antibody, in patients with advanced EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC).
Authors: Jin-Ji Yang, Nick Pavlakis, Fan Xie, Yi-Long Wu
Journal: Journal of Clinical Oncology (2023)

e21085 Background: GB263T, a novel trispecific antibody directed against EGFR and cMET, adopts the design of two humanized VHH antibodies that recognize two different cMET epitopes, in which a conformational change induced by the first VHH binding exposes the second epitope for the second VHH to bind. Sequential binding of the two VHH antibodies to cMET increases tumor specificity, which results in widening of the safety window. In vitro studies show that GB263T induces better antigen-antibody molecular endocytosis, more completely blocks the signal transduction pathway, and has better ADCC activity compared to a benchmark. In addition, GB263T has demonstrated promising pre-clinical activity in models with various EGFR/cMET alterations. Here, we report the preliminary dose escalation results of the first-in-human phase I/II study of GB263T in patients (pts) with advanced EGFRm NSCLC (NCT05332574). Methods: This multicenter (China and Australia), phase I/II study was conducted using an accelerated titration method followed by a traditional 3+3 design for dose escalation. Pts with EGFRm NSCLC with prior EGFR TKI and platinum-based chemotherapy were enrolled. GB263T was given at 140-1680 mg (5 dose cohorts) IV weekly for the first two 28-day cycles and biweekly thereafter. Objectives were to evaluate the safety and tolerability, determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D), and assess the pharmacokinetics, immunogenicity, and preliminary efficacy of GB263T. Results: As of Feb 7, 2023, 6 pts were treated: 140mg (n = 1), 420mg (n = 1), 840mg (n = 3), 1260mg (n = 1). The enrolment of the 1260mg cohort is ongoing. All pts had received previous third-generation EGFR-TKI and platinum-based chemotherapy. Medium treatment duration was 49.5 days (range 2-113). No DLTs were observed. Five (83.3%) pts experienced treatment-related AEs (TRAEs), and all TRAEs were mild (grade 1/2): infusion related reaction (n = 3, 50%), rash (n = 2, 33%), mouth ulcer (n = 1, 17%), fatigue (n = 1, 17%), GGT increased (n = 1, 17%), ALP increased (n = 1, 17%) and direct bilirubin increased (n = 1, 17%). There were no treatment-related discontinuations. Among five response-evaluable pts, three (60%) achieved stable disease (SD). Tumor shrinkage was observed in all three SD pts, with a maximum reduction of 17% in the target lesion. All three SD pts remained on treatment at data cutoff. Conclusions: Results to date demonstrate a favorable safety profile with early signal of clinical activity. Continued dose escalation and clinical investigation of GB263T is ongoing. Updated data will be presented. Clinical trial information: NCT05332574 .
Healthcare coverage, access, and affordability among adult immigrant cancer survivors in the United States.
Authors: Patricia Mae Garcia Santos, Justin Michael Barnes, Kanan Shah, Leticia M Nogueira, Robin Yabroff, Fumiko Chino
Journal: Journal of Clinical Oncology (2023)

6529 Background: Cancer is a leading cause of morbidity and mortality among US immigrants; however, barriers to care remain understudied. This study assessed disparities in health insurance, health care access, and affordability among immigrant cancer survivors in the United States. Methods: Adult cancer survivors aged ≥18 years who participated in the 2019-2022 National Health Interview Survey were classified as 1) natives 2) foreign-born (FB) citizens or 3) noncitizens. Logistic regression tested for associations between nativity/citizenship and insurance, access (i.e., urgent care, emergency room [ER], hospital admissions), and affordability (assessed by social determinants of health [SDoH]: financial hardship, food insecurity, housing assistance). Separate models adjusted for demographics, socioeconomic status, and comorbidities. Results: A total of 8,923 adults (90% natives, 7% FB citizens, 3% noncitizens) were included in the study. There were baseline differences in age &lt;65 (42% natives vs 61% FB citizens vs 76% noncitizens), female sex (57% vs 59% vs 73%), non-White race (15% vs 64% vs 77%), and Hispanic ethnicity (31% vs 62% vs 5%) between groups (all p&lt;0.05). More noncitizens had household incomes &lt;125% of the federal poverty line (12% vs 18% vs 35%). On adjusted analysis, noncitizens were 3x as likely as natives to be uninsured (2.99 [1.36-6.53]; p=0.006) and FB citizens were 2x as likely to have Medicaid (2.10 [1.35-2.35]; p=0.001). Financial hardship was 1.5x more common among FB citizens (1.50 [1.18-1.91]; p&lt;0.001) while receipt of housing assistance was &gt;2x more common among FB citizens (2.98 [1.82-4.88]; p&lt;0.001) and noncitizens (2.37 [1.08-5.22]; p=0.03). While more FB citizens (18%) and noncitizens (33%) were food insecure (vs. 11%), there were no associations with nativity/citizenship (Table). There were no significant differences in health care access across groups. Conclusions: In this nationwide analysis of adult cancer survivors, although there were no differences in health care access/utilization, immigrants and foreign-born citizens had higher rates of uninsurance and affordability concerns—suggestive of barriers to care. This may portend worse health outcomes in cancer survivorship. [Table: see text]
Real-world treatment patterns of bruton tyrosine kinase inhibitors (BTKi) in patients with mantle cell lymphoma (MCL) in community oncology practices in the United States (US).
Authors: Bijal D. Shah, Mei Xue, Keri Yang, Sizhu Liu, Boxiong Tang
Journal: Journal of Clinical Oncology (2023)

e19525 Background: Real-world data on BTKi use in MCL remain limited. This study aimed to examine US real-world BTKi treatment pattern, duration, and adherence in MCL patients. Methods: This retrospective observational study used electronic medical records (EMR) data from Integra Connect database in 18 US community-based oncology practices. Adults with MCL diagnosis on ≥2 separate dates who started BTKi therapy between 1/1/2019 and 11/30/2021 were included. EMR data was collected to ensure adequate medical history and ≥6-months follow up period. Index date was defined based on the use of one of the 3 BTKi: zanubrutinib, acalabrutinib, and ibrutinib for 3 BTKi patient cohorts. Baseline comorbidities were collected ≤90 days prior to index date based on diagnosis records. Sociodemographic and clinical characteristics, comorbidities, and treatment patterns were examined by each BTKi group. Treatment duration was calculated based on EMR and claims until end of follow up. Discontinuation data was based on unstructured physician notes. Kaplan-Meier analysis was used to compare treatment duration between the 3 BTKi groups. Results: In 402 MCL patients identified to start BTKi therapy (44 zanubrutinib; 161 acalabrutinib; 197 ibrutinib), the median age (range) at BTKi therapy start was 75 (56-89) years in zanubrutinib, 76 (36-89) in acalabrutinib, and 72 (36-89) in ibrutinib group ( P&lt;0.01; Table). There is no significant difference between the 3 BTKi groups in other baseline characteristics. Half of zanubrutinib patients used other BTKi in prior therapy, with 31.8% switched from other BTKis to zanubrutinib ≤60 days of treatment start. In acalabrutinib group, 29% had prior BTKi use. Given a later approval date, zanubrutinib group had a relative shorter mean follow-up period (493 days [d]) vs acalabrutinib (701 d) and ibrutinib (746 d). Nevertheless, zanubrutinib patients had significantly longer median treatment duration (292 d) vs acalabrutinib (259 d) and ibrutinib (149 d) ( P&lt;.01). Conclusions: Real-world EMR data from US community-based oncology practices suggested significantly longer treatment duration and adherence in MCL patients treated with zanubrutinib compared with acalabrutinib or ibrutinib. Further analyses on long term utilization are needed upon data maturation. [Table: see text]